Saikosaponins ameliorate hyperlipidemia in rats by enhancing hepatic lipid and cholesterol metabolism. (6th April 2023)

• Record Type: Journal Article
• Authors: Zheng, Qi; Li, Xiaojiaoyang; Huang, Nana; Li, Fanghong; Ge, Junde; Wang, Daijie; Sun, Rong; Liu, Runping
• Is Part Of: Journal of ethnopharmacology. Volume 305(2023)
• Publication Date: 2023-04-06
• Subjects: Saikosaponins -- Hyperlipidemia -- Lipids -- Cholesterol metabolism -- Metabolomics -- Transcriptomics; ApoA1 apolipoprotein A-I -- ApoB100 apolipoprotein B-100 -- BAs bile acids -- Cer ceramides -- CM chylomicrons -- CVDs cardio-cerebrovascular diseases -- DALs altered lipid metabolites -- DEGs differentially expressed genes -- ELISA enzyme-linked immunosorbent assay -- ETC electron transport chain -- FA fatty acid -- GlcCer glucosylceramides -- GO Gene Ontology -- GSEA Gene Set Enrichment Analysis -- HDL-C high-density lipoprotein cholesterol -- HFD high-fat diet -- LC/MS liquid chromatography/mass spectrometry -- LDL-C low-density lipoprotein cholesterol -- Lpa lipoprotein (a) -- NAFLD non-alcoholic fatty liver disease -- PC phosphatidylcholine -- PE phosphatidylethanolamine -- PG phosphatidylglycerols -- PPARα peroxisome proliferator-activated receptor alpha -- RB Radix Bupleuri -- RNA-Seq RNA sequencing -- SIM simvastatin -- SR-B1 scavenger receptor class B member 1 -- SREBP-1c sterol regulatory element-binding protein 1c -- SSs saikosaponins -- TC total cholesterol -- TCM traditional Chinese Medicine -- TG triglyceride -- TNF-α tumor necrosis factor-alpha -- VLDL-C very-low-density lipoprotein cholesterol; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.116110
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Hyperlipidemia is the systemic manifestation of abnormal lipid metabolism, characterized by elevated circulating levels of cholesterol and triglyceride and a high risk of cardiovascular events. Radix Bupleuri (RB) is a traditional Chinese herbal product used to treat liver diseases. Our previous study demonstrated that Saikosaponins (SSs), the most potent bioactive ingredients in RB, ameliorate hepatic steatosis. However, whether SSs have anti-hyperlipidemia effects and plausible underlying mechanisms remain elusive. Aim of the study: To comprehensively evaluate the lipid-lowering potential of SSs against hyperlipidemia in rats. Materials and methods: RNA sequencing and untargeted metabolomics approaches were applied to analyze the changes in the liver transcriptome and serum lipid profile in long-term high-fat diet feeding-induced hyperlipidemia rats in response to SSs or positive drug simvastatin (SIM) intervention. Results: Our data revealed that SSs significantly alleviated HFD-induced hypertriglyceridemia and hypercholesterolemia. Combined with the analysis of gene ontology enrichment analysis and gene set enrichment analysis, we found that SSs remarkably repaired the unbalanced blood lipid metabolic spectrum in a dose-dependent manner by increasing the hepatic uptake of circulating fatty acids and facilitating mitochondrial respiration in fatty acid oxidation, comparable to SIM group. In addition, SSs markedly modulated cholesterol clearance by promoting intracellular cholesterol efflux, HDL remodeling, LDL particle clearance, and bile acid synthesis. SSs also efficiently protected the liver from lipid overload-related oxidative stress and lipid peroxidation, as well as substantially exaggerated inflammatory response. Conclusion: Our research not only unraveled the intricate mechanisms underlying the lipid-lowering functions of SSs but also provided novel perspectives on developing an SSs-based therapeutic strategy for the treatment of hyperlipidemia. Classification: Metabolism. Graphical abstract: Image 1 Highlights: SSs ameliorate hyperlipidemia by enhancing blood lipid transport and clearance. SSs promote HDL-induced efflux and BA synthesis to reduce blood cholesterol. SSs improve hepatic oxidative stress and inflammation in hyperlipidemia rats.